Bone marrow-derived mononuclear cells promote improvement in glomerular function in rats with early diabetic nephropathy

Cell Physiol Biochem. 2013;32(3):699-718. doi: 10.1159/000354473. Epub 2013 Sep 13.

Abstract

Background/aims: Diabetic nephropathy is one of the main causes of end-stage renal disease. The present study investigated the effect of mononuclear cell (MC) therapy in rats subjected to diabetic nephropathy.

Methods: Male Wistar rats were divided into control (CTRL), diabetic (DM), CTRL+MC and DM+MC groups. Diabetes was induced by a single injection of streptozotocin (45 mg/kg, i.p.) and, 4 weeks later, 2×10(7) MCs were injected via the jugular vein.

Results: The rats in the DM and DM+MC groups showed increased glycemia, glomerular filtration rate and glomerular tuff area versus control groups. The glomerular filtration rate and glomerular tuff area were normalized in the DM+MC group. No alterations were observed in the fractional excretion of electrolytes and proteinuria between the DM and DM+MC groups. TGF-β1 protein levels in the DM group were significantly increased versus control animals and normalized in the DM+MC group. An increase in ED1(+)/arginase I(+) macrophages and IL-10 renal expression was observed in the DM+MC group versus DM group.

Conclusions: Bone marrow-derived MC therapy was able to prevent glomerular alterations and TGF-β1 protein overexpression and modulated glomerular arginase I(+) macrophage infiltration in rats subjected to early diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginase / metabolism
  • Blood Glucose / analysis
  • Body Weight
  • Bone Marrow Cells / cytology*
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / surgery*
  • Diabetic Nephropathies / surgery*
  • Ectodysplasins / metabolism
  • Glomerular Filtration Rate
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • Kidney / pathology
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / transplantation*
  • Macrophages / metabolism
  • Male
  • Proteinuria
  • Rats
  • Rats, Wistar
  • Transforming Growth Factor beta1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Blood Glucose
  • Ectodysplasins
  • Interleukin-6
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • Interleukin-10
  • Arginase
  • arginase I, rat